Borna disease virus (BDV) is a neurotropic virus that causes an immune-mediated syndrome resulting in disturbances in movement and behaviour. Originally the disease was described as a natural infection of horses in a small city, Borna, in Southeast Germany.
Borna disease (BD) is an infectious disease of the central nervous system characterized by profound behavioural abnormalities, inflammatory cell infiltrates and the accumulation of disease-specific antigens in limbic system neurons. Naturally occurring infections with Borna disease virus (BVD), the etiological agent of Borna disease, have been confirmed mainly in horses and sheep. The disease can, however, be experimentally transmitted to a wide range of animal species including rodents and nonhuman primates with variable clinical and pathological manifestations. Recent epidemiological data suggest that Borna disease may be more widespread in a subclinical form. It is possible that Borna disease virus is involved in human disorders of the central nervous system. Therefore, it is important to have a reliable diagnostic test system and an effective treatment.
Borna disease virus has not been fully characterized yet, however, the genome of cell adapted Borna disease virus (BDV)-strains have been cloned and sequenced by Cubitt et al. [J. Virol. 68, p. 1382-1396 (1994)] and Briese et al. [Proc. Natl. Acad. Sci., USA, vol. 91, p. 4362-4366 (May 1994)].
BDV contains a nonsegmented negative-sense 8.9 kb RNA-genome with complementary 3' and 5' termini. Subgenomic RNAs have been mapped to the viral genome and some of them found to undergo posttranscriptional modification by RNA splicing. The features known up to now seem to indicate that BDV represents the prototype of a new group of animal viruses within the order Mononegavirales.
BDV is strictly neurotropic and disseminates by intra-axonal transport from the site of infection. The virus replicates in vitro in embryonic brain cells of various animal species. Cocultivation of such brain cells with various permanent cell lines such as MDCK or Vero cells results in a persistent infection. Infectivity is mainly cell associated, the virus is noncytopathic and spreads by cell to cell contact. Intracellular viral antigen can be demonstrated in the cell nucleus and cytoplasm of infected cells. Morphologically the virion appears to be a 60-90 nm enveloped, spherical particle containing an electron dense internal structure.
BDV replication in cells is associated with the presence of at least three virus-specific antigens with molecular weight of 18 (gp18), 24 (p24) and 38/40 (p38 or p40) kilodaltons. An enzyme-linked immunosorbent assay for detecting antibodies to Borna disease virus specific proteins is described by Briese et al. (Journal of Clinical Microbiology, 33, p. 348-351 (February 1995)]. The ELISA test described by Briese uses the proteins p38/40, p23 and gp18 which are found in vitro and in vivo in the nucleus and cytoplasm of infected cells. The recombinant proteins used in the ELISA assay of Briese were produced by using a cell-adapted laboratory BDV strain from persistently BDV-infected MDCK cells.
The disadvantage of the known ELISA test is that only a few BDV proteins are used and therefore not all infections of Borna disease virus can be reliably detected.